Contributed by Joshua Grill, PhD
On Thursday, December 5, attendees at the Clinical Trials in Alzheimer’s Disease (CTAD) Conference heard more from Biogen about its recently resurrected drug, aducanumab (see previous Blog). New data were presented that were consistent with what had previously been shared. Biogen claims that a single positive Phase 3 trial of aducanumab and a secondary analysis of data from a second, negative Phase 3 trial suggest a benefit among patients receiving the highest dose for the full duration of the study (18 months). In both cases, high dose aducanumab appeared to slow the rate of disease progression by 10-25%, depending on the clinical measurement. Notably, the presentation included new data on a very small number of participants who underwent tau PET imaging (a way of measuring the presence of neurofibrillary tangles in the brain), and found that aducanumab also lowered the rate of tau accumulation.
Many questions remain unanswered, including some critical ones about the methods used in Biogen’s analyses, as thoughtfully outlined in Lancet Neurology this week by our colleague at USC, Dr. Lon Schneider. One particularly interesting aspect relates to participants who were discontinued from the trial because of side effects related to aducanumab. The important step was taken to try to keep participants in the trial, even if they were no longer able to take the medication. Those participants were almost certainly healthier than their counterparts who did not continue in the study, however, and they now knew that they had received the active medication, creating a unique risk for bias.
Other questions include:
- Did the drug work as well in those with dementia compared to those with Mild Cognitive Impairment (both were included in the study)?
- Did the data differ globally? The trial was conducted in 20 countries.
- And, of course the billion dollar question – will these data will be enough for the FDA to approve aducanumab?
Dr. Grill is an Associate Professor of Psychiatry & Human Behavior and Neurobiology & Behavior at the University of California, Irvine. He is the Director of UCI MIND and Associate Director of the UCI Alzheimer’s Disease Research Center (ADRC). He also directs the Outreach, Recruitment, and Engagement Core for the ADRC and is leads the Accrual and Retention Consult Service for the UCI Institute for Clinical and Translational Science. His research is currently focused on clinical trials across the spectrum of Alzheimer’s disease. He has published a number of important findings on trial design, recruitment and retention, and research ethics.